A single tumor is able to induce several different functional types of immune response (blocking, cytotoxic, etc.). We propose to define each of these functional responses in terms of binding characteristics, and to identify and isolate the tumor cell determinants associated with the various functional responses. Immunological enhancement as a regulator of cell-mediated anti- tumor immunity will be examined in an in vitro sensitization system. Human lymphocytes will be sensitized on tumor cells from HLA-identical siblings or on HLA-haploidentical fibroblasts; mouse lymphocytes will be sensitized on syngeneic tumor cells. The ability of blocking sera to inhibit the generation of cytotoxic lymphoid cells in these systems and the mechanism of this inhibition will be studied. The mechanism of enhancement will also be studied in vivo with a syngeneic methylcholanthrene-induced murine sarcoma. Bibliographic references: Appel, S.H., Almon, R.R., and Levy, N.L.: Acetylcholine Receptor antibodies in Myasthenia Gravis. New Engl. J. Med. 293:760, 1975. Levy, N.L., Seigler, H.F. and Singleton, W.W.: A Multiphase Immunotherapy Regimen for Human Melanoma -- Clinical and Laboratory Results. Cancer 35: 1548, 1974.